Touhami Mahjoub, Anis Haddad, Mariam Al-Mutawa, Wael Bahia, Wassim Y Almawi, Faouzi Janhani, Aymen Soua, Ramzi R. Finan
To investigate the association of progesterone receptor (PGR) gene variants with the susceptibility to recurrent pregnancy loss (RPL).
Retrospective case-control study.
Outpatient obstetrics/gynecology clinics.
Women with RPL (396), defined as ≥3 consecutive miscarriages of unknown etiology, and 361 control women.
PGR genotyping was done by allelic exclusion method (real-time PCR).
Main outcome measures
PGR SNPs and the distribution of their alleles, genotypes and haplotypes.
Higher minor allele frequency (MAF) of rs590688, rs10895068, and rs1942836 was seen in RPL cases than in control women, which remained significant after controlling for multiple comparisons. Significantly higher frequencies of heterozygous (1/2) rs608995, along with heterozygous (1/2) and homozygous (2/2) rs590688, rs10895068, and rs1942836 genotype carriers were seen between RPL cases versus control women, respectively, which persisted after controlling for age, BMI, and menarche. Increased risk of RPL associated with rs590688 and rs1942836 was dependent on the number of minor alleles, thus suggesting a “dose-dependent” effect associated with both variants. Varied linkage disequilibrium (LD) was noted between rs590688, rs10895068, rs608995, and rs1942836 PGR variants associated with RPL. Increased frequency of CGTC, and reduced frequency of GGAT haplotypes was noted in women with RPL compared to control women, thereby assigning RPL susceptible and protective nature to these haplotypes, respectively. This association persisted after controlling for multiple comparisons, and adjusting for covariates.
This confirms positive association of specific PGR variants (rs590688, rs10895068, and rs1942836), and PGR haplotypes (ATGCCGTC, ATTCGGTC) with increased risk of RPL, thereby supports role for PGR as RPL candidate locus.
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